Principles of Drug Excretion

Excretion/Elimination

Refers to the processes by which a drug/drug metabolite is eliminated from the body

Kidneyy

The primary organ for drug excretion

glomerular filtration

Occurs at the level of the nephron and works by pushing water and small molecules through a tuft of capillaries, similar to pushing things through a sieve

glomerular filtration

All drugs not bound to plasma proteins are filtered.

glomerular filtration

Elimination of drugs by the kidneys is best quantified by the renal clearance.

renal clearance

Elimination of drugs by the kidneys is best quantified by the —

Cp= plasma concentration

Cu= urinary concentration

Vu= the rate of flow of urine

given of renal clearance

active tubular secretion

In the proximal portion of the renal tubule, active transport mechanisms exist for both acidic and basic drugs.

In the proximal portion of the renal tubule, active transport mechanisms exist for both acidic and basic drugs.

Passive tubular reabsorption

Only lipid-soluble drugs are reabsorbed in this manner.

carnivores ; acidic (pH 5.5–7.0) ; basic drugs

Urinary pH of carnivore animals is — , therefore — exist in the ionized form and are more readily excreted.

passive tubular reabsorption

Urinary pH of carnivore animals is acidic (pH 5.5–7.0), therefore basic drugs exist in the ionized formand are more readily excreted.

herbivore ; 7.0-8.0 ; acidic drugs

Urinary pH range of — animals is —, therefore — drugs exist in the ionized form and are more readily excreted

passive tubular reabsorption

Urinary pH range of herbivore animals is 7.0–8.0,therefore acidic drugs exist in the ionized form andare more readily excreted

enterohepatic recycling

Both the parent drug and glucuronide form of the drug may be eliminated via the bile.

parent drug and glucuronide ; bile

Enterohepatic Recycling: Both the — of the drug may be eliminated via the —

enterohepatic recycling

Drugs that are attached to glucuronic acid and removed through bile can be broken down by enzymes (β-glucuronidase) from gut bacteria.

glucuronic acid ; bile ; B-glucuronidase

Enterohepatic Recycling: Drugs that are attached to — and removed through — can be broken down by enzymes (—) from gut bacteria.

mammary excretion

Drugs given to the dam appear in the milk andproduce residues, requiring a withdrawal period ifthe milk is to be used for human consumption

residues ; withdrawal period

Drugs given to the dam appear in the milk and produce — , requiring a — if the milk is to be used for human consumption

mammary excretion

Milk is acidic relative to plasma; therefore, basicdrugs tend to exist in higher concentrations in milkthan in plasma (ion trapping)

acidic ; basic ; higher

mammary excretion: Milk is — relative to plasma; therefore, — drugs tend to exist in — concentrations in milk than in plasma (ion trapping)

salivary excretion

Important in herbivores receiving parenteral antimicrobial drugs

salivary excretion

Swallowing antimicrobial-laden saliva may disrupt the ruminal microflora.

expiration

Primarily important for volatile drugs such as gas anesthetic drugs.

minor routes

Tears

Sweat